Myelofibrosis treatment sequencing: mutation-informed risk and optimal JAK inhibitor discontinuation.

INTRODUCTION

Myelofibrosis (MF) is a heterogeneous myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, and risk of leukemic transformation. As therapeutic options expand, treatment discontinuation and sequencing are increasingly recognized as clinically relevant determinants of patient outcomes.

AREAS COVERED: A literature search was performed using PubMed/MEDLINE and major hematology conference proceedings (ASH and EHA), covering publications from January 2010 through February 2026. This review discusses mutation-informed risk stratification, current and emerging JAK inhibitor treatment sequencing strategies, and practical approaches to treatment discontinuation and therapeutic transition in MF.

EXPERT OPINION: Optimizing outcomes in MF increasingly requires proactive transition management rather than reactive treatment interruption. Early identification of treatment failure, phenotype-guided therapeutic sequencing, and integration of molecular risk assessment may improve long-term disease management and could contribute to better clinical outcomes, although prospective confirmation remains necessary.